One of the effects of wide-spread abuse of cocaine is the appearance of "cocaine babies" in nurseries. These infants have an increased prevalence of cerebral infarcts, and neurological/behavioral abnormalities. No one yet knows the long-term outcome of these children. A new problem is emerging in the west with the recent advent of smokable methamphetamine ("ice"). A preliminary report describes methamphetamine-exposed infants as having more severe abnormalities than those exposed to cocaine. The long-term prospect for these children is even more uncertain. This research is aimed at investigating the developmental effects of exposure to methamphetamine. High doses of methamphetamine are known to be neurotoxic to adult rats, causing reductions in striatal dopamine and serotonin. In preliminary research we have found that pregnant rats tolerate high doses of methamphetamine better than males, but postnatally a high incidence of anophthalmia/microphthalmia is observed in the offspring. More recently, abnormalities of the retina were observed in offspring not exhibiting eye reduction defects. The aims of this research are to: (1) characterize the neurotoxic and ocular effects of prenatal and neurotoxic effects of neonatal exposure to methamphetamine in rats; (2) to test the hypothesis that such exposures induce irreversible reductions to developing striatal dopaminergic and/or serotonergic systems as evidenced by changes in locomotor behavior (especially circling and by use of dopaminergic and serotonergic drug challenges), passive avoidance, spontaneous alternation, startle reactivity and Morris maze; and (3) to test the hypothesis that these effects will occur at doses below those inducing ocular teratogenicity in the prenatal studies. Striatal and hippocampal dopamine and serotonin will be measured as will maternal serum methamphetamine levels and embryonic/fetal/neonatal brain concentrations. Critical period effects will be investigated and dose-response relationships developed at each stage of development investigated. The racemic compound (D,L-methamphetamine) will be compared to the D-isomer under both prenatal and postnatal exposure conditions. Pair-fed/pair-watered controls for possible body weight and nutritional confounding effects will be included in addition to ad lib fed controls in order to rule out the contribution of these variables to the effects obtained. Experiments testing for maternal carry-over effects of prenatal drug exposure on postnatal rearing will be conducted using a fostering/crossfostering design. The data are intended to provide information on the long-term effects on developing mammals of exposure in utero or neonatally to methamphetamine. A future goal is to compare the developmental effects of methamphetamine to that of related drugs.